Hunt in Forests of Borneo Aims to Track Down Natural Drugs

By PHILIP SHENON

Published: December 6, 1994

KUCHING, Malaysia—
DOWN a steep gravel path and over a wooden bridge shaded by a curtain of towering eucalyptus trees, visitors to this stretch of the Borneo rain forest run into a guarded, fenced-off area several hundred feet wide. It is filled with thousands of leafy, ankle-high tree seedlings that, at first glance, look about as significant as a row of backyard shrubs. The nursery is marked with two signs. The larger, printed in red, bears a warning to intruders: Restricted Area.

The other sign identifies the species of this smooth-barked tree -- Calophyllum lanigerum -- which is tantalizing a team of scientists from the United States and Malaysia. They are trying to determine if, when fully grown, these seedlings and other trees that flourish in the rain forests of Southeast Asia could offer a cure for AIDS.

Initial reports from the laboratories of the National Cancer Institute in Frederick, Md., show that a substance in the leaves of Calophyllum lanigerum destroys H.I.V., the virus that causes AIDS, without killing healthy cells. "This extract from this Calophyllum species has shown some significant activity in our AIDS screening," said Dr. Gordon Cragg, chief of the natural products branch of the National Cancer Institute, whose office directs American-funded efforts around the world to locate natural medicines.

Dr. Cragg is careful not to overstate the significance of the discoveries made so far in the dense rain forests of Borneo, the Southeast Asian island that is divided among Malaysia, Indonesia and the tiny oil-rich nation of Brunei. "So far everything has happened only in a test tube," he said, noting that the research here has so far not been widely publicized -- and for good reason. "This absolutely doesn't mean that we're going to show activity in a human being. In many instances, something that might look promising in a test tube just bombs out."

At the same time, scientists here and in the United States are exhilarated because, after years of scavenging in the Asian rain forests for magic bullets, they are now beginning to turn up promising leads in the search for an AIDS treatment, if not a cure, from trees and plants. Environmentalists are excited by the prospect that important pharmaceutical discoveries could provide a financial incentive to preserve rain forests that are threatened by rapacious logging. "That's what excites me -- the implications of this," said Dr. Djaja J. Soejarto, a botanist at the University of Illinois in Chicago, whose team identified the Malaysian tree under a grant from the National Cancer Institute. Even if the Calophyllum tree proves to be of no use as an AIDS treatment, he said, the discovery suggests that there are similar substances to be found in the forest that will be effective.

Only a small fraction of the plant species in Borneo have been tested so far. "We're demonstrating that these compounds do exist in the rain forest," he said. "This is why the rain forest must be preserved." The material isolated from the Malaysian tree, which has been called Calanolide A, is now being tested on mice at the laboratories of the National Cancer Institute. Three other substances -- extracts from a related gum tree in the Borneo jungle, a rare vine found in the West African nation of Cameroon and a shrub native to western Australia -- are also being tested on animals, having shown initial success against the AIDS virus in laboratory tests. Human testing is likely to be years away, if it occurs at all, depending on the results of the animal experiments.

So far, the National Cancer Institute has had no luck searching the rain forest for a cure for a cancer. The natural-products program has identified two anticancer agents, but both came from the sea. One was found in a sponge taken from near the coast of the Philippines, the other in seaweed discovered in the waters off New Zealand. These agents are being tested in the laboratory. While the National Cancer Institute has been evaluating natural substances for their medical use since the early 1960's, the comprehensive Government-financed search for drugs in the rain forest began only eight years ago. The actual gathering of plant material was contracted out to scientists at the University of Illinois, the New York Botanical Garden and the Missouri Botanical Garden in a $3.6 million program. The three institutions divided the globe, and Dr. Soejarto's team in Illinois is responsible for the rain forests of Borneo and the rest of Southeast Asia.

In the search for natural drugs, rains forests are considered the most promising natural environments for research because of the vast diversity of life that they shelter. More than half of the world's estimated 250,000 species of plants live in tropical forests, yet less than 10 percent have ever been tested for their ability to cure disease. "In a single acre of rain forest you may be able to find hundreds of different species of trees, and from them you may be able to generate 10,000 different chemical compounds, the result of millions of years of evolution in the forest," said Dr. Soejarto.

The Illinois team has spent years in Borneo collecting bags of leaves, bark and resin samples and sending them to the National Cancer Institute for testing. At the Institute's laboratories the samples are frozen -- to kill hitchhiking insects -- and then broken down with solvents to be tested against human immune cells, lymphocytes, that have been infected with the AIDS virus. If an extract shows promise against the virus without killing off the cells, scientists begin the laborious process of reducing the extract to its chemical components, and then testing each of them against the virus.

In 1987, a member of the Illinois team took samples from a smooth-barked gum tree found in a swamp in the Borneo jungle. It was later identified as Calophyllum lanigerum. Four years later, the National Cancer Institute alerted Dr. Soejarto that its testing showed that Calophyllum lanigerum was effective against H.I.V.-1, the strain of the AIDS virus most common in the Western world, and that his team should go back to Malaysia and take more samples. After an initial alarm -- the team returned to find that the original tree had been chopped down, with only a stump left behind -- similar trees were found several miles away, including the thousands of seedlings that have since been moved to a central area for cultivation. And Dr. Soejarto discovered a second species that produced a substance similar to Calanolide A.

If the Malaysian rain forests do offer a cure for AIDS or any other disease, the National Cancer Institute has already guaranteed that Malaysia will share any proceeds with pharmaceutical companies. For its part, the provincial government of Sarawak, the Malaysian state where the Calophyllum trees were found, has banned logging of the species, a critical step given how much of the rain forests of Sarawak have already been ravaged by the timber industry. "If there's a superstar drug somewhere in the rain forests, it would be worth billions of dollars," said Dr. Soejarto. "Surely if we can provide that kind of revenue, there would be every reason to preserve the rain forest."

Photo: Tree seedlings at Botanical Research Center in Sarawak on the island of Borneo, cultivated in the hope that a leaf substance will help fight AIDS. (Stuart Isett for the New York Times) Map of Indonesia showing location of Borneo.